Jul 13, 2018 9:00:00 AM
Summary of Mirea, A et al; IL-1 Family Cytokine Pathways Underlying NAFLD: Towards New Treatment Strategies. Trends in Molecular Medicine 2018; Volume 24, Issue 5, Pages 458-471 . For the full article, click here.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Eventhough underlying mechanisms are not fully understood, pahways responsible for the activation of inflammatory cytokines like TNF and members of the IL-1 cytokine family are key in the development of NAFLD. Recent studies reported that not only the inflammasome-caspase-1 pathway is responsible for the activation of proinflammatory cytokines: neutrophil serine proteases (NSPs) are as well. This opinion article describes new insights about the NSPs as potent cytokine activators that contribute to liver disease progression.
Alpha-1-antitrypsin (AAT) is a natural occuring serine peptidase inhibitor produced by the liver of both inflammasome-dependent and independent cytokine activation pathways. It is the most abundant circulating protease inhibitor known. It mainly targets enzymes released by neutrophils, especially neutrophil elastase (NE) but also proteinase 3 (PR3) and Cathepsin G (CG). These NSPs are stored in the azurophilic granules of neutrophils. When neutrophils are activated, NSPs will be released and can activate for example proinflammatory cytokines. In the extracellular matrix AAT can inhibit NSPs and this leads to the inhibition of cytokine activation. A deficit of AAT is responsible for insufficient inhibition of NSPs and thus for inflammation-induced liver diseases. In patients, AAT has already been shown to be a succesful therapy in COPD and cystic fybrosis: Administration of AAT in patients with COPD or cystic fybrosis has proven efficient in inhibiting neutrophil elastase activity in the lung function.
Since AAT is a potent inducer of IL-1Ra it is a reason to consider that this protein is a good candidate for treating IL-1-mediated diseases.
Jun 14, 2018 5:00:00 PM
Summary of Arafat, S. et al; Elevated neutrophil elastase in tears of ocular graft-versus-host disease patients. American Journal of Ophthamology Apr 2017. Click here for the full article.
Graft-versus-host disease is a systemic complication and major cause of morbidity and mortality in patients that have undergone a transplantation procedure. It is a complex disease that involves an interplay between the donor and recipient adaptive and innate immune systems and potentially affects a variety of tissues depending on the type of transplant. Ocular graft-versus-host disease (oGvHD) occurs in 40-60% of all recipients and can be seen in up to 90% of patients with chronic GvHD. Neutrophil elastase (NE) is an important multi-functional enzyme predominantly released by neutrophils. Besides its antimicrobial role, NE also activates cellular receptors (TLRs) and is considered to be one of the most destructive enzymes owing its ability to degrade almost all components of the extracellular matrix.
The purpose of this study was to compare neutrophil elastase levels in tears of oGvHD patients with normal subjects. 14 oGvHD patients and 14 matched normal controls were enrolled in the study. Neutrophil elastase (cat. # HK319) was measured from tear washes of both eyes. The results demonstrated that NE-levels of oGvHD patients were 250-fold higher in comparison to the matched controls. Secondary markers such as MPO, MMP-8 and MMP-9 were also significantly elevated in the oGvHD group. This study shows that NE can be a potential marker of ocular inflammation. However, the effectiveness of NE as an inflammatory biomarker remain unkown. Large, well-designed prospective studies are needed to test the effectiveness of an NE assay.
May 15, 2018 2:00:00 AM
Summary of Gupta, S. et al; Urinary antimicrobial peptides: potential novel biomarkers of obstructive uropathy. Journal of Pediatric Urology 2018. Click here for the full article.
Antimicrobial peptides (AMPs) have historically been evaluated for their role in protecting against uropathogens. However, AMPs have not been evaluated for expression in noninfectious urological injury such as urinary tract obstruction. The objective of this pilot study is to compare urinary AMP expression in children undergoing surgical intervention for ureteropelvic junction obstruction (UPJO) with non-obstructed controls.
Thirty bladder urine samples were obtained from children with UPJO and compared with matched controls on AMP levels of LL-37 (Cat. # HK321), NGAL (Cat. # HK330), HIP/PAP, BD-1 and HD-5. The results demonstrated that urinary AMP levels were significantly higher in UPJO patients than controls (NGAL and LL-37 both with a P-value of <0.001). The biological significance of increased urinary AMP levels in children with urinary tract obstruction remains unclear, but it is likely a reflection of the urothelial and tubular stress resulting from obstructive uropathy. It may further represent an adaptive mechanism of uroepithelial barrier function or protect against infection during urinary stasis. However, this should be confirmed by future studies on AMP expression as a biomarker of uroepithelial injury.
Apr 19, 2018 3:00:00 AM
Summary of Wang, T. et al; Plasma neutrophil elastase and elafin as prognostic biomarker for acute respiratory distress syndrome: a multicenter survival and longitudinal prospective observation study. SHOCK Aug 2017. Click here for the full article.
Acute respiratory distress syndrome (ARDS) is a complicated clinical syndrome with a high mortality rate that is characterized by non-cardiogenic pulmonary edema and acute respiratory failure. In the lung an imbalance between the proteinases and their inhibitors damages the alveolar-capillary barrier, resulting in the leaking of protein-rich fluid into the interstitium and alveolar spaces, which is the key pathophysiological characteristic of ARDS. Previous studies have suggested that circulating elastase and elafin could be used to predict acute lung injury or ARDS development. However, whether they can be used as an early marker for the mortality and severity of ARDS is still unclear.
This study examines the association between neutrophil elastase and elafin with the mortality and severity of ARDS. A total of 167 ARDS patients were enrolled. Plasma samples were collected from each patient within the first day, third day and on the seventh day of ARDS development. Plasma elastase and elafin levels were assayed using an elafin ELISA kit (Cat. # HK318) and an elastase ELISA kit (Cat. # HK319). The results among the three time points demonstrated that elastase levels were significantly higher and elafin levels were significantly lower in non-survivors, indicating elastase as a risk factor and elafin as a protective factor for ARDS mortality. The markers combined also showed a better ARDS mortality prediction in comparison to the current prediction methods (APACHE II score and Berlin criteria). Based on these findings the paper concludes that circulation levels of elastase an elafin may have the potential to predict ARDS mortality and better inform clinicians about mortality risk.
Mar 22, 2018 8:00:00 AM
Summary of Kopczynska, M. et al; Complement system biomarkers in first episode psychosis. Schizophrenia Research, Dec 2017. Click here for the full article.
There has been debate over the past few years about the criteria currently used to classify patients with psychiatric disorders. The lack of objective and quantitative diagnostic criteria means that we rely on symptom-based categorization when deciding on patient classification and less on the underlying biology. Accumulating evidence suggests that inflammation and the immune system is the cause of such psychiatric disorders. The complement system is one such system, particularly the classical pathway, that potentially could be an important contributor.
Complement is a key driver of inflammation and complement dysregulation causes pathology in many diseases. The goal of this study was to investigate the potential for using complement-related proteins as serum biomarkers with prognostic and/or theranostic value. The concentrations of eleven complement analytes were measured using ELISA in 136 first episode psychosis (FEP) patients and 42 controls. Of the eleven analytes measured only one was significantly different between FEP and control populations, namely TCC.
The findings suggest that measurement of selected complement analytes interrogating the classical pathway could contribute to the early diagnosis of psychosis. A large study, planned prospectively, minimizing sample bias and using appropriately collected and stored EDTA plasma samples, is needed to confirm and extend the findings.
Mar 1, 2018 4:30:00 AM
Summary of Zelek, W. et al; Measurement of soluble CD59 in CSF in demyelinating disease: evidence for an intrathecal source of soluble CD59. Mutiple Sclerosis, Feb 2018. Click here for the full article.
Activation of complement via the classical, lectin or alternative pathway leads to the formation of C3 convertase complexes that cleave C3 to C3a and C3b. C3b causes C5 convertase, which ultimately causes formation of the membrane attack complex (MAC) responsible for cell lysis. CD59 regulates formation of MAC by preventing recruitment of C9.
This study investigates the role of sCD59 in patients with demyelinating disorders. Cerebrospinal fluid (CSF) and matching plasma samples were taken from 78 patients with a demyelinating disorder and 34 from healthy controls. The concentration of sCD59 in these samples was measured using the Hycult Biotech sCD59 ELISA (HK374). An interesting finding was that sCD59 levels in CSF were approximately double those in matched plasma. The results further demonstrated that there was no significant difference in sCD59 levels between the various disease groups.
To determine the source of sCD59 in CSF, the study further performed immunohistochemical staining of brain sections. These results demonstrated that the choroid plexus is likely a site of abundant expression in the brain and may be a site of immune activation.
Whether the (relatively) high amounts of sCD59 in CSF are of any functional relevance remains to be demonstrated. In principle, sCD59 might contribute to homeostasis by dampening down complement activation in the CSF, but it is not a biomarker of demyelinating diseases.
Jan 25, 2018 4:00:00 AM
Summary of Westra, D. et al; Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome. Pediatric Nephrology 2017, 32(2). Click here for the full article.
The role of complement in the atypical form of hemolytic uremic syndrome (aHUS) has been extensively studied. However, less is known about the role of complement in infection-induced HUS. In a majority of these cases, the disease is triggered by an infection with Shiga-like toxin-producing Escherichia coli (STEC-HUS). Based on the similarity of the clinical manifestations of complement-mediated and infection-induced HUS, this study hypothesizes that also here the dysregulation of the complement system has an important place in the pathogenesis.
To determine the role of the alternative complement pathway (AP), 37 pediatric patients were enrolled in this study. 26 patients had STEC-HUS and 11 were diagnosed with aHUS. EDTA plasma was taken from the patients and used for testing a variety of complement factors and components, such as C3, CFH, CFI and TCC (Cat. # HK328). Results show that TCC was only significantly increased in STEC-HUS patients in the acute phase […] making it useful in monitoring the course of the disease. Taken all aspects together it is clear that measuring AP activation products, in particular C3d/C3 ratio, might help in monitoring disease activity and distinguishing between the different HUS etiologies. The exact role of altered complement activation in the pathogenesis of STEC-HUS, however, has not been fully elucidated.
Dec 6, 2017 2:30:00 AM
Summary of Treskes, N. et al; Diagnostic accuracy of novel serological biomarkers to detect acute mesenteric ischemia: a systematic review and meta-analysis. Internal and Emergency Medicine 12:6, 2017. Click here for the full article.
Acute mesenteric ischemia (AMI) is a rare but devastating medical condition with high mortality rates. Laparotomy remains the golden standard for diagnosis of AMI, but it is often unhelpful or too late. This meta-analysis aims to evaluate the diagnostic accuracy of novel serological biomarkers, including I-FABP. Thirteen studies containing 1,435 patients were examined in which I-FABP was used as a biomarker. The pooled sensitivity and specificity are 79.0% and 91.3% respectively.
Nov 10, 2017 7:00:00 AM
Oct 4, 2017 2:00:00 AM
Summary of Yamashiro, K et al; Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke. PLOS ONE 2017. Click here for the full article.
Metabolic disorders are one of the leading causes for heart disease and stroke. Increasing evidence suggests that dysbiosis is associated with metabolic diseases, but there is little known on the relation with ischemic stroke.
The aim of this study was to investigate whether the gut microbiota […] are altered in patients with ischemic stroke. Blood samples of 41 ischemic stroke patients were measured on a variety of metabolic readouts, but also cytokines and acute phase proteins were tested such as LBP (Cat. # HK315). Fecal samples were additionally used to examine the gut microbial composition with qPCR.
The results show that stroke patients had an impaired composition of the fecal bacteria and an elevated organic acid concentration. However, there were no differences in LBP concentrations, TNF-α levels and bacteremia rates between the patients with stroke and the control subjects.
Despite these findings, the data still suggests that gut dysbiosis in patients with ischemic stroke is associated with host metabolism and inflammation. Further studies are needed to determine a more predictive indicator of ischemic stroke.